Because of the importance of optic nerve lesions in humans, studies are proposed for the creation and investigation of laboratory models of optic nerve disease. Previous studies from this laboratory have shown the feasibility of the rat for studies of this kind and there is now adequate baseline data on the anatomy and histochemistry of the rat optic nerve. Rats will be used exclusively in the studies. In all the experimental optic neuropathies light microscopy, electron microscopy and histochemistry will be used. An effort will be made to determine the mechanism by which cyanide produces optic nerve lesions. A comparison of histochemical and histologic lesions will be made. The relationship of vascular patterns in the optic nerve to the sites of lesions will be determined. The neuropathy of ethambutol intoxication will be investigated and an attempt also made to determine the mechanism by which this agent damages the anterior visual system. Emphasis will be placed on possible changes in divalent ions in relation to the sites of lesions. Lead intoxication will be studied in animals chronically intoxicated with this metal. The effects of nickel intoxication will be studied in order to gain insight into the possible role of 5'nucleotidase in the function of the adult optic nerve.